In situ decellularization of a large animal saccular aneurysm model: sustained inflammation and active aneurysm wall remodeling
AuthorsKing, Robert M.
Langan, Erin T.
Leporati, Anita M.
Raskett, Christopher M.
Puri, Ajit S.
Gounis, Matthew J.
Bogdanov, Alexei A. Jr.
UMass Chan AffiliationsDepartment of Radiology, Laboratory of Molecular Imaging Probes
Department of Radiology, New England Center for Stroke Research
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AbstractOBJECTIVE: To investigate in situ decellularization of a large animal model of saccular aneurysm as a strategy for achieving aneurysmal growth and lasting inflammation. METHODS: 18 New Zealand White rabbits were randomized 2:1 to receive endoluminal sodium dodecyl sulfate infusion (SDS, 1% solution, 45 min) following elastase or elastase-only treatment (control). All aneurysms were measured by digital subtraction angiography every 2 weeks. Every 2 weeks, three of the rabbits (two elastase + SDS, one control) underwent MRI, followed by contrast injection with myeloperoxidase (MPO)-sensing contrast agent. MRI was repeated 3 hours after contrast injection and the enhancement ratio (ER) was calculated. Following MRI, aneurysms were explanted and subjected to immunohistopathology. RESULTS: During follow-up MRI, the average ER for SDS-treated animals was 1.63+/-0.20, compared with 1.01+/-0.06 for controls (p < 0.001). The width of SDS-treated aneurysms increased significantly in comparison with the elastase aneurysms (47% vs 20%, p < 0.001). Image analysis of thin sections showed infiltration of MPO-positive cells in decellularized aneurysms and surroundings through the 12-week observation period while control tissue had 5-6 times fewer cells present 2 weeks after aneurysm creation. Immunohistochemistry demonstrated the presence of MPO-positive cells surrounding decellularized lesions at early time points. MPO-positive cells were found in the adventitia and in the thrombi adherent to the aneurysm wall at later time points. CONCLUSIONS: In situ decellularization of a large animal model of saccular aneurysms reproduces features of unstable aneurysms, such as chronic inflammation (up to 12 weeks) and active aneurysm wall remodeling, leading to continued growth over 8 weeks.
King RM, Caroff J, Langan ET, Leporati A, Rodriguez-Rodriguez A, Raskett CM, Gupta S, Puri AS, Caravan P, Gounis MJ, Bogdanov AA Jr. In situ decellularization of a large animal saccular aneurysm model: sustained inflammation and active aneurysm wall remodeling. J Neurointerv Surg. 2020 Oct 5:neurintsurg-2020-016589. doi: 10.1136/neurintsurg-2020-016589. Epub ahead of print. PMID: 33020207. Link to article on publisher's site